Many drugs with substantial in vitro biological activity lack therapeutic efficacy in vivo because of poor aqueous solubility. The rate at which a drug dissolves in vivo from a particular dosage form is often the limiting step in determining absorption and often is strongly correlated with the therapeutic efficacy of the drug.
Lipid-based liquid formulations (e.g., liposomes and/or vesicles) have been used to deliver poorly soluble or insoluble small molecule therapeutics with poor bioavailability, particularly anticancer agents (Campbell et al., U.S. Pat. No. 6,680,068; Asvar et al. U.S. Pat. No. 6,689,381, Bernstein et al., U.S. Pat. No. 6,423,345; Knight et al., U.S. Pat. No. 5,049,388; Radhakrishnan et al., U.S. Pat. No. 4,895,719). Typically, in liposomes and/or vesicles the small molecule therapeutic agent is sequestered in an aqueous core surrounded by lipid. Accordingly, such formulations are usually administered intravenously or by inhalation.
Advantages associated with lipid-based formulations include inertness, superior toxicity profiles and safe handling. Lipid-based dispersions where amphipathic or hydrophobic compounds are effectively solubilized in aqueous solution by dissolution in lipid bilayer matrices are potentially very valuable since the drug may potentially be administered orally, intraperitoneally and intranasally as well as intravenously or by inhalation with increased bioavailability. Accordingly, what is needed are lipid-based formulations which facilitate delivery and increase bioavailability, particularly via oral administration of amphipathic or hydrophobic drugs. These novel formulations will typically increase the bioavailability of the amphipathic or hydrophobic drug.